Insight into mosquito GnRH-related neuropeptide receptor specificity revealed through analysis of naturally occurring and synthetic analogs of this neuropeptide family

Adipokinetic hormone (AKH), corazonin (CRZ), and the AKH/CRZ-related peptide (ACP) are neuropeptides considered homologous to the vertebrate gonadotropin-releasing hormone (GnRH). All three Aedes aegypti GnRH-related neuropeptide receptors have been characterized and functionally deorphanized. Individually they exhibit high specificity for their native ligands, prompting us to investigate the contribution of ligand structures in conferring receptor specificity for two of these receptors. Here, we designed a series of analogs based on the native ACP sequence and screened them using a heterologous system to identify critical residues required for ACP receptor (ACPR) activation. Analogs lacking the carboxy-terminal amidation, replacing aromatics, as well as truncated analogs were either completely inactive or had very low activities on ACPR. The polar threonine (position 3) and the blocked amino-terminal pyroglutamate are also critical, whereas ACP analogs with alanine substitutions at position 2 (valine), 5 (serine), 6 (arginine), and 7 (aspartate) were less detrimental including the substitution of charged residues. Replacing asparagine (position 9) with an alanine resulted in a 5-fold more active analog. A naturally-occurring ACP analog, with a conserved substitution in position two, was well tolerated yet displayed significantly reduced activity compared to the native mosquito ACP peptide. Chain length contributes to ligand selectivity in this system, since the endogenous octapeptide Aedae-AKH does not activate the ACPR whereas AKH decapeptides show low albeit significant activity. Similarly, we utilized this in vitro heterologous assay approach against an A. aegypti AKH receptor (AKHR-IA) testing carefully selected naturally-occurring AKH analogs from other insects to determine how substitutions of specific residues in the AKH ligand influence AKHR-IA activation. AKH analogs having single substitutions compared to Aedae-AKH revealed position 7 (either serine or asparagine) was well tolerated or had slightly improved activation whereas changes to position 6 (proline) compromised receptor activation by nearly 10-fold. Substitution of position 3 (threonine) or analogs with combinations of substitutions were quite detrimental with a significant decrease in AKHR-IA activation. Collectively, these results advance our understanding of how two GnRH-related systems in A. aegypti sharing the most recent evolutionary origin sustain independence of function and signaling despite their relatively high degree of ligand and receptor homology.York University Librarie

American Muslims: The Untouchables of American Constitutional Democracy?

This article is about the future of Muslims in the American constitutional democracy. How this future will look like depends highly on how the dominant majority as well as those sitting in the political, executive and judicial branches of power will deal with the emergence of Islamophobia. This article explores the roots of American fear of Muslims and their faith and reflects on what Islamophobia and its reinforcement bring for the future of American democracy. This article contends that the American anxiety about Islam will create huge disparities and advance a political agenda tainted with animus toward Muslims. This insidious dis-invitation to Muslims to participate in the American democracy needs to be halted to cleanse the American political scene from anxiety, bigotry and exclusion

Characterization of the Adipokinetic Hormone/Corazonin-Related Peptide Signalling System in the Mosquito, Aedes Aegypti

The adipokinetic hormone/corazonin-related peptide (ACP) is an insect neuropeptide structurally intermediate between corazonin (CRZ) and adipokinetic (AKH) hormones, which all demonstrate homology to the vertebrate gonadotropin-releasing hormone (GnRH). AKH and CRZ are best known to function in energy mobilization and cardioacceleration, respectively, however, the function of the ACP signalling system remains unclear. Here the gene encoding the ACP receptor in Aedes aegypti has been identified. Functional deorphanization of AedaeACPR-I revealed a highly specific response for its native ligand, ACP. Analysis of spatial and developmental expression profiles reveals enrichment of ACP and ACPR in the central nervous system and post-eclosion, respectively. The cell-specific distribution of the ACP and ACPR within the central nervous system was examined revealing expression within distinct regions of the brain, thoracic ganglia, and abdominal ganglia. The findings of this thesis point to a role of ACP within the nervous system functioning either as a neuromodulator or neurotransmitter

The Constitutional Dynamics of Religious Manifestations: on Abstraction from the Religious Dimension

The justification grounds for a special right to religious freedom have been scrutinized in the public and the scholarly debates across liberal democracies. In the public debate, the legal admissibility of some religious manifestations has been challenged for reasons that suggest religious manifestations have been favored in law qua religious. In the scholarly debate, the focus has been on the “specialness” of religion and the justification grounds for singling out religion qua religion for a favored treatment in law. However, recent developments show that religion has also been singled out qua religion for a disfavored treatment. This project pays attention to both angles of the debate on law and religion. To this end, it combines the outcomes of six separate articles, each touching upon a different aspect of this debate. As such, it elaborates in the first four articles on the question whether religion qua religion deserves special legal solicitude. Subsequently, it explores in the last two articles on singling out religion qua religion for a disfavored treatment in law

Freedom of Religion and Living Together

Despite the international recognition of religious freedom as a fundamental human right, recent developments in the United States and Europe reveal that the Islamic faith has been singled out qua Islam for special prohibitions. The question is whether this sectarian approach is compatible with the normative liberal approach to religious freedom that emphasizes egalitarianism and neutrality. The answer to this question is, no. Although religion within the paradigm of liberal political philosophy does not warrant special legal protection qua religion, this article contends that it is equally troublesome to single out religion qua religion for special disfavored treatment, even if the justification is facially neutral. This article uses facially neutral examples, such as: the French burqa-ban case, the Travel Ban project of President Trump, and the anti-Sharia debacle in the state of Oklahoma. This article draws on the dichotomous approach of liberal political philosophy to religion and develops a non-sectarian framework of arguments to defend religious liberty

THEMATIC CLASSIFICATION OF RELIGIOUSLY-MARKED PHRASEOLOGICAL UNITS

The article deals with a thematic analysis of religiously-marked phraseological units (RMPU) that reflect Religious World Picture (RWP), an inseparable constituent of both conceptual and linguistic world pictures. The selection of phraseological units is premised by two criterions, namely, etymological aspect and the presence of a religious component. Throughout data collection process in the focus of our interest have been only phraseological units that etymologically can be traced back to the Bible and phraseological units with religious components that bear semantic reference to religious entities. The classification embraces the notions, such as universally recognized religious values, ritually-ceremonial patterns and dogmas, supernatural conceptions, moral values reflecting personal, intellectual and social characteristics of an individual. Each group, in turn, is divided into a number of subgrouping